Cryptococcosis is the most frequent life-threatening fungal infection of patients with AIDS and the first manifestation of AIDS in many of these patients. The etiology of cryptococcosis in patients with AIDS, as well as most patients without AIDS, is Cryptococcus neoformans var. neoformans serotype A. Preliminary studies have established that strains of C neoformans serotype A vary in several properties of potential pathobiological importance. Studies of strains of C. neoformans serotype A from patients with AIDS and from patients without AIDS will continue to be compared with previously characterized strains and mutants. The proposed biological and biochemical investigations will elucidate the determinant(s) of pathogenicity. In the previous period of grant support, the susceptibility of strains to nonspecific host defense mechanisms were compared. Lewis rat alveolar macrophages (AMos) and human peripheral blood neutrophils, monocytes and natural killer cells were evaluated for the abilities to phagocytize and/or kill selected strains of C. neoformans. The initial defense mechanism against cryptococcosis, the interaction of yeast cells with AMos, was scrutinized in vitro with methods that dissected the processes of attachment, ingestion and killing. The effects of no serum, normal and immune serum on these processes were also evaluated. The size, structure, and antiphagocytic properties of the capsular polysaccharides of different strains were also examined and compared. In this proposal, strains of C. neoformans from patients with and without AIDS will be compared for virulence. The mechanism(s) of killing of yeast cells by AMos and other cells will be investigated, and the basis for the resistance of some strains to killing will be explored. Strains that differ in biological and chemical characteristics will be biotyped by comparing the base sequences of their ribosomal genes.